Ma `lumot

Mitradatlar - zaharga qarshi immunitet rivojlanyaptimi?


Afsonaga ko'ra, Mithridates barcha ma'lum toksinlarni sinchkovlik bilan o'rganib chiqdi va tekshirdi va mahbuslarni gvineya cho'chqalari sifatida ishlatib, potentsial vositalarni sinab ko'rdi. Taxminlarga ko'ra, Mitridatning mehnatlari o'z samarasini berdi, chunki ko'plab qadimgi mualliflar, shu jumladan Pliniy Elder, u barcha aniqlangan toksinlar uchun universal antidot yaratgan va muntazam ravishda iste'mol qilgan va u mitridat (mitridatium) nomi bilan mashhur bo'lgan.

Aytishlaricha, u immunitetni oshirish uchun oz miqdorda zahar yutgan.

Umumiy zahar bo'ladimi yoki har bir turni birma -bir qabul qiladimi, bu sizning tanangizni umuman zahar/zahar/toksinlarga qarshi turishga yoki immunitetga ega bo'lishga qodirmi?


SE ga xush kelibsiz. Tartibga solish: Javob toksinning ta'sir mexanizmiga asoslangan ikki qismdan iborat. Hurmatli: @David va @jamesqf

Immunitet

Tanadagi oq qon hujayralari o'z-o'zidan yoki o'z-o'zidan bo'lmagan peptidlarni tanib olish uchun mas'uldir va immunitet tizimining moslashuvchan bo'linmasini hosil qiladi. B -limfotsitlar turli xil peptidlarni bog'laydigan retseptorga ega. Tanadagi begona peptidlarni tanib bo'lgach, ular reaksiyadan (somatik gipermutatsiya) o'tib, begona peptidga xos bo'ladi. Ular, shuningdek, begona peptidni zararsizlantiradigan boshqa oqsilni (antikorlarni) yashiradigan plazma hujayralariga bo'linadi.

O'limga olib kelmaydigan, lekin B hujayralari reaktsiyasini qo'zg'atadigan etarli miqdordagi konsentratsiyada immunologik "xotira" paydo bo'ladi. Bu xotira reaksiyaga nisbatan bir xil peptidga tezroq javob berishga imkon beradi. Bu tanaga toksik peptidning yuqori konsentratsiyasiga bardosh berishga imkon beradi, aks holda uni zararsizlantirish o'limga olib kelishi mumkin edi.

Vaktsinalar bunga juda yaqin printsip asosida ishlaydi.

Gomeostaz

Har bir toksin qandaydir biologik jarayon bilan o'zaro ta'sir qiladi va uni muvozanatdan chiqaradi. Tana faol ravishda muvozanatni qandaydir vositalar bilan tiklashga harakat qiladi.

Misol uchun, agar ligand tugagan bo'lsa, organizm ta'sirga qarshi turish uchun retseptorlar sonini ko'paytirishi mumkin va aksincha.

Tana oz miqdordagi toksinlarni qabul qilib, muvozanatni juda oz miqdorda mos ligandlar yoki retseptorlari kontsentratsiyasini sozlashi mumkin.

Shunga qaramay, bu jarayonni boshdan kechirgan odam, o'tmagan odamga qaraganda, toksinning yuqori dozasiga bardosh bera oladi.


"Super kalamushlar" standart zaharlarga genetik immunitetni rivojlantiradilar

Haddersfild universiteti olimi Buyuk Britaniyani odatdagi zaharlardan himoyalanuvchi "o'ta kalamushlar" vayron qiluvchi muammosi haqida ogohlantirdi. Uning tadqiqotlari butun mamlakat bo'ylab qiziqish uyg'otdi, ayniqsa Angliyaning g'arbiy qismida, bu erda kalamushlarning 75 foizi chidamli turi bo'lishi mumkin.

Doktor Dugi Klark, Xaddersfild universitetining Amaliy fanlar maktabining biologiya fanlari bo'limi boshlig'i, Buyuk Britaniyadagi rodentitsidlarga qarshilik xaritasini yaratish loyihasini boshqaradi. Mamlakat bo'ylab yuzlab kalamushlardan DNK namunalari olinadi, qaysi hududlarda genetik mutatsiyaga ega bo'lgan kalamushlarning eng ko'p tarqalganligini aniqlash uchun ularni eng ko'p ishlatiladigan kalamush zaharlaridan himoya qiladi.

Maqsad, mamlakatning qaysi hududlarida eng ko'p qo'llaniladigan kemiruvchilarga - warfarin, bromadiolon va difenakumga genetik qarshilikka ega kalamushlarning eng ko'p populyatsiyasiga ega ekanligini aniqlashdir. Bu antikoagulyantlar bo'lib, kalamushlarni ichki qon ketishidan o'ldiradi va 1950 -yillardan buyon keng qo'llanila boshlangan, lekin ular kiritilgandan ko'p o'tmay, ba'zi kalamushlarga bu zaharlar ta'sir qilmaganligi aniqlandi.

1950-yillarda ba'zi kalamushlar an'anaviy zaharlarga bardosh bera olishi birinchi marta ma'lum bo'lgach, hukumat tadqiqot o'tkazdi. Ammo buni kalamushlarni tuzoqqa tushirish va butun hayvonni boqish sinovlarini o'tkazish usuli bilan qilish kerak edi. Ushbu tadqiqot 1990-yillarda to'xtatildi, ammo so'nggi yigirma yil ichida kalamushlarda qarshilik muammosi ortdi.

Hayvonlar ko'paygan joyda ular kasallik tarqalishi, oziq-ovqat resurslarini yo'qotishi, elektr kabellarini kemirishi va hatto strukturaga zarar etkazishi mumkin. Va ular tirik qolganlari uchun ularning avlodlari ham xuddi shunday qarshilikka ega. Doktor Klarkning aytishicha, natija shundaki, dastlab ba'zi shahar va qishloqlarda chidamli kalamushlarning atigi bir necha foizi bo'lishi mumkin edi, hozir ular aholining katta qismini tashkil qiladi.

Hozirgi vaqtda Angliyaning janubi va G'arbiy mamlakatning 70 % dan ko'prog'i "super" kalamush turiga mansub ayrim hududlarda eng ko'p tarqalgan.

Bu shuni anglatadiki, jonzotlar populyatsiyasi ko'payadi va hayvonlar va hatto uy mushuklari uchun xavf tug'dirishi mumkin, ular kalamushlarni ovlab, yutib yuboradi, ularning tanasi ularga chidamli bo'lgan zaharni olib ketadi.

Muammoga qarshi kurashish uchun kuchliroq zaharlar mavjud - brodifakum va flokumafen - ulardan foydalanish mumkin va ular hatto super kalamushlar deb ataladiganlarga qarshi ham samarali ekanligini isbotladi. Ammo bu kemiruvchilarni Sog'liqni saqlash va xavfsizlik bo'yicha ma'muriyat litsenziyasi ostida qat'iy nazorat qilinadigan sharoitda ishlatish kerak. Shu sababli, mahalliy hokimiyat organlari, zararkunandalarga qarshi kurashuvchi operatorlar va kalamush zaharlarini ishlab chiqaruvchi kimyoviy gigantlar mamlakatning qaysi hududlarida chidamli kalamushlar ko'proq zararlanganini bilishlari kerak, shunda kuchliroq moddalardan foydalanishga yashil chiroq yoqilishi mumkin.

"Bir hududda biz tahlil qilgan har bir kalamush chidamli edi va zararkunandalarga qarshi kurash shu qadar yomon ediki, zararkunandalarga qarshi kurash kompaniyasi sog'liqni saqlash va xavfsizlik boshqarmasiga kuchliroq kemiruvchi vositalardan favqulodda foydalanish uchun murojaat qildi va ular ikki hafta ichida yo'q qilindi".

Qarshilikni keltirib chiqaradigan genetik mutatsiyalar aniqlanishi natijasida doktor Klark va uning hamkasblari Evropaning zararkunandalarga qarshi kurashuvchi etakchi kompaniyalari (BASF, Bayer, Bell, Killgerm, PelGar) tomonidan moliyalashtiriladigan yirik yangi tadqiqot loyihasini boshladilar. , Syngenta), Britaniya zararkunandalariga qarshi kurash tashkiloti va zararkunandalarga qarshi kurash bo'yicha milliy uyushma. Tadqiqot tirik hayvonlardan foydalanish o'rniga, hayvonning genetik tarkibini tahlil qilib, uning kalamush dumining uchidan uch sm uzunlikdagi oddiy zaharlarga chidamli yoki yo'qligini aniqlaydi.

Maqsad kamida 600 ta hayvonni sinovdan o'tkazishdir va loyiha 2013 yilda yakunlanadi deb umid qilinmoqda. Qishki ob -havoning kelishi, kalamushlarning tabiiy oziq -ovqat bilan ta'minlanishining ko'p qismini talon -taroj qilib, universitetga yuboriladigan namunalar sonini tezlashtiradi. Haddersfild laboratoriyalari.

Tadqiqotning asosiy maqsadi Buyuk Britaniyada bir qancha qaynoq nuqtalarga qaratilgan bo'lib, u erda chidamli kalamushlar ustunligi ma'lum yoki shubha qilingan.

"Super kalamush" atamasi juda mos keladi, deydi doktor Klark. Oddiy zaharlardan ta'sirlanmagan jonzotlar kemiruvchi kimyoviy moddalar ta'sirida DNK mutatsiyasiga uchraganligi sababli chidamli bo'lolmadi. Buning uchun vaqt oralig'i juda qisqa. Buning o'rniga ular kemiruvchilarning zaharlaridan himoya qiladigan tabiiy genetik mutatsiyaga ega. Vaqt o'tishi bilan kalamushlarni nazorat qilish uchun ushbu zaharlar bilan ishlov beriladigan hududda sezgir "oddiy" kalamushlar va genetik jihatdan chidamli "super" kalamushlarning aralash populyatsiyasi bilan populyatsiya faqat qarshilik genini o'tkazadigan "super" kalamush turiga aylanadi. avlod.

U ko'proq ilmiy ma'lumotlarni to'plaganida, topilmalar 2013 yil davomida e'lon qilinadi. Ammo, uning tadqiqotlari haqidagi yangiliklar, ayniqsa, Angliyaning g'arbiy qismida, umuman, 75 foizni tashkil etishi mumkin. kalamushlarning chidamli turi hisoblanadi.


Ba'zi sichqonlar tabiiy, ammo juda g'ayrioddiy evolyutsiya orqali zaharlanishga qarshi immunitetga ega bo'lishdi

Sichqonlar zo'r (qarang: yuqori chidamli sichqonlar, laboratoriyada o'stirilgan sun'iy organlarga ega sichqonlar, Isroilning bomba hidlaydigan xavfsizlik sichqonlari), lekin ba'zida siz ularni kvartirangizda / uyingizda / nonvoyxonada / oshxonada / Nyu-York metro stantsiyasida xohlamaysiz, shuning uchun siz oddiy kemiruvchilar zahari bo'lgan warfarin sotib olishingiz mumkin. Biroq, ba'zi sichqonlar g'ayrioddiy usullar bilan bu zaharga qarshi immunitetni ishlab chiqdilar: genlarni gorizontal o'tkazilishi, gibridlanish evolyutsiyasi, bu faqat ilgari mikroblarda kuzatilgan.

Ning joriy sonida xabar berilganidek Hozirgi biologiya, Nemis nonvoyxonasidagi sichqonlar, hatto do'stimiz uy sichqonchasi uchun o'pish bo'lgan, ayniqsa, yomon formadagi warfarinni ishlatishga hech qanday munosabat bildirmaganligi aniqlandi. Genetik tahlil shuni ko'rsatdiki, o'sha oshxonadagi sichqonlarda, odatda, O'rta er dengizining qumli g'arbiy sohillari atrofida topilgan, uy sichqonchasining alohida (bir -biri bilan chambarchas bog'liq) turi bo'lgan Jazoir sichqonchasining DNKining katta qismi bor edi.

Jazoir sichqonchasi, ko'ryapsizmi, warfaringa qarshi immunitetga ega, ko'rinib turibdiki, bu gen, shuningdek, K vitamini tanqisligini boshqarishga yordam beradi, Jazoir sichqonchasining dietasi va odamlar, bizning barcha sayohatlarimiz va shunga o'xshashlar bilan, odatda, bu ikki turni kiritdilar. bir-biri bilan aloqada bo'lgan. Uy sichqonchasi Jazoir sichqonchasi bilan o'stirildi va bam: zaharli immunitetli super uy sichqonlari.

Gibridizatsiya foydali genetik tuzilishga olib keladigan bunday evolyutsiyaga gorizontal gen o'tkazilishi deyiladi. Bu foydali mutatsiyalar keyingi avlodga o'tadigan evolyutsiyaning odatiy uslubidan juda farq qiladi va aslida hech qanday murakkab hayvonda hech qachon kuzatilmagan. Gorizontal gen uzatilishi shu paytgacha faqat mikroblarda kuzatilgan, shuning uchun uni sichqondek murakkab va ajoyib narsada ko'rish juda hayratlanarli. Albatta, bu novvoylar va MTA xodimlari uchun o'z korxonalarini va/yoki metro bekatlarini kemiruvchilardan tozalashni qiyinlashtirishi mumkin, lekin sichqonlar bundan xursand bo'lishadi.


Shohlikni egallash

Taxminan miloddan avvalgi 116 yilda Mithridates yashirinib chiqib, onasi bilan to'qnash keldi. Yosh podshoh onasini taxtdan muvaffaqiyatli olib tashladi va uni qamoqqa tashladi va u oxir oqibat vafot etdi. Uning hukmronligi davrida, Laodikiya Mithridatesning ukasi Mithridates Xrestni yaxshi ko'rar edi, ehtimol u o'z akasiga qaraganda irodasiga ko'proq moyil edi. U ham, ehtimol, onasi qamalganidan ko'p o'tmay, voqea joyidan g'oyib bo'ldi. Bitta taklifga ko'ra, Mitridat onasi va ukasini o'ldirgan.

Bu raqiblar yo'ldan ozgani uchun Mitridat Pont qirolligining yagona hukmdori bo'ldi.

Keyin Mitridatlar marhum otasining ekspansionistik siyosatining davomi sifatida shohligini kengaytira boshladi. Miloddan avvalgi 115/114 yillarda yosh qirol Qrimdagi ellinistik aholi punktlari va ularning skif qo'shnilari o'rtasida bo'layotgan mojaroga aralashish uchun Qora dengizni kesib o'tdi.

Herakl sifatida Pont podshohi Mitridat VI ning byusti. Marmar, Rim imperiyasi davri (1-asr). ( CC BY 3.0 )

Buning natijasida ellinistik aholi punktlari Mitridatning himoyasi evaziga mustaqilliklarini unga topshirdilar. Mithridatesning keyingi maqsadi Pontusning sharqiy qo'shnisi Paflagoniya edi, u miloddan avvalgi 108/107 yilda Bitiniya qiroli Nikomed III Euergetes yordamida egallagan.

Garchi Rim elchisi Paflagoniya qiroli Astreodonni taxtiga qaytarishga harakat qilgan bo'lsa -da, uning urinishlari behuda ketdi. Buning o'rniga, Nikomedning o'g'li qo'g'irchoq shohi sifatida Paflagon taxtiga o'tirdi.

Miloddan avvalgi 104/103 yillarda Kolxida (hozirgi G'arbiy Gruziya) Mitridatlar mulkiga qo'shildi va Mitridatlar o'z saltanatini kengaytirishda davom etdi. Paflagoniyaning Mitridatlar va Nikomedlar tomonidan bosib olinishi va birinchisining zabt etilishi Rim Senati tomonidan deyarli ijobiy baholanmagan.

Pont podshohligi xaritasi, Mitridat VI hukmronligidan oldin (quyuq binafsha rang), uning fathlaridan keyin (binafsha rang), birinchi Mitridatik urushlardagi g'alabalari (pushti) va Pontning ittifoqchisi Armaniston Qirolligi (yashil). ( Jamoat domeni )

Shunday bo'lsa-da, rimliklar o'sha paytgacha bu voqealarga unchalik qiziqmagan. Bunga ma'lum omillar, jumladan, Rim allaqachon qatnashgan urushlar va Rim va Anadoluni ajratib turgan masofa sabab bo'lgan.


Mithradates - Zaharga qarshi immunitetni rivojlantirasizmi? - Biologiya

2) Muayyan moddaga "hujum qilish" qobiliyati immunitet deb nomlanadi va birgalikda immun tizimi deb ataladigan ma'lum bir differentsiatsiyalangan hujayralar to'plamining faoliyati natijasida yuzaga keladi.

3) Agar hujum qilingan material o'z-o'zidan zararli bo'lmasa, immunitet hujumining yon ta'siri materialning bevosita ta'siridan ko'ra yoqimsizroq bo'lsa, biz immunitet hujumining oqibatlarini "allergiya".
(Kimdir o'zini "zaharli pechakka qarshi immunitet" deb da'vo qilsa, ular nimani anglatadi?)

    Pernicious anemiya - B12 vitaminini o'zlashtiradigan ferment hujumga uchraydi
    Ko'p skleroz - asab aksonlari atrofidagi miyelin qobig'i hujumga uchraydi
    Revmatik isitma -- yurak klapanlarining hujayradan tashqari matritsasi hujumga uchraydi
    Lupus eritematozi -- kollagen, DNK va boshqa hujayra tarkibiga hujum qilinadi
    Myasthenia Gravis -- mushak hujayralaridagi atsetilxolin retseptorlari hujumga uchraydi
    Erkaklar bepushtlikdan keyin bepushtlik - sperma birinchi marta balog'at yoshida shakllanadi!

5) Immunitetning asosiy qismi (eng yaxshi tushunilgan qismi) - "antikorlar" deb nomlangan maxsus oqsillar sinfining qoniga va boshqa suyuqliklarga sintezi va sekretsiyasi. Ular immunoglobinlar deb ham ataladi, chunki ular globinlar deb ataladigan qon oqsillarining bir qismidir. Xususan, ular gamma-globulinlar deb ataladigan kichik to'plamni tashkil qiladi.

6) Har bir antikor molekulasida 2 ta (yoki IgMda 10 ta) bog‘lanish joyi (fermentlar kimyoviy substratlari bilan bog‘langan faol joylarga o‘xshash) mavjud bo‘lib, ular orqali antikor molekulalari boshqa molekulalar to‘liq huquqqa ega bo‘lgan har qanday molekula bilan juda aniq va juda qattiq bog‘lanadi. bu bog'lash joyiga mos keladigan shakl. Antikor bog'laydigan molekula uning "antijeni" deb ataladi. Antigen so'zining aniq etimologiyasi antikor sintezi qandaydir tarzda uning faol joylari bog'langan antigen tomonidan qo'zg'atilganligini anglatadi, ammo bu har doim ham to'g'ri emas. Yangi "epitop" so'zi ma'lum bir antikor bog'laydigan molekulyar joyni anglatadi.

7) Antikor molekulalarining tegishli antigen epitopi uchun o'ziga xosligi juda katta bo'lishi mumkin. Fermentlarning substratlari o'ziga xosligi singari, antikorlarni bog'lashning o'ziga xosligi ham ikki shakl o'rtasida aniq mos kelishidan kelib chiqadi. Tajribali biologlar ko'pincha hujayralar ichidagi ma'lum molekulalarning joylashishini aniqlash uchun bu o'ziga xoslikdan foydalanadilar. Qiziqarli antijenga "qarshi" antikorlar paydo bo'ladi, qarzga olinadi yoki sotib olinadi va lyuminestsent kimyoviy moddalar keyinchalik bu antikorlarga kovalent tarzda bog'lanadi, shunda ularning joylashishini "immunofluoresans mikroskopi" yordamida kuzatish mumkin. Zamonaviy homiladorlik testlari, shuningdek, aniqligi endokrinologiyada inqilob qilgan "radioimmun tahlillari" kabi, ba'zi oqsil gormonlariga antikorlarning bog'lanish xususiyatiga bog'liq.

8) Antikorlar B-limfotsit deb ataladigan ma'lum turdagi oq qon hujayralari tomonidan sintezlanadi (ko'pincha oddiy B-hujayralar deb ataladi). Ular sekretsiya paytida ularni "plazma hujayralari" deb ham atashadi.

9) (asosiy fakt) Har bir individual B -limfotsit (va uning barcha qiz hujayralari bo'linib ketganda) o'ziga xos o'ziga xos xususiyatga ega antikor molekulalarini chiqaradi. Bu hujayra va uning aka -ukalari sintez qiladigan va chiqaradigan barcha antikor molekulalari aynan bir xil shaklli bog'lanish joylariga ega bo'ladi va bir xil antijenlarga yoki epitoplarga bog'lanadi. B-hujayra klonlarining faqat bitta bog'lanish o'ziga xosligi bilan cheklanishi, ehtimol, bizning immun tizimimiz mexanizmi haqidagi eng muhim faktdir! Buni tushunganingizga ishonch hosil qiling!

10) B -limfotsitlar (yoki aniqrog'i, ularning prekursor hujayralari) o'sish va bo'linish, shuningdek, antikor molekulalari sekretsiyasi oshishi bilan "o'z" antijeni (ularning antikorlari bog'lanadigan) molekulalariga ta'sir qilishiga javob beradi. Ushbu stimulyatsiya jarayoni patogenlarni o'ldirish uchun etarli miqdorda antikor ishlab chiqarish uchun bir necha kun davom etishi mumkin. Aslida, bu stimulyatsiya va javob - bu yuqumli kasallikdan davolanishni boshlash uchun bir necha kun davom etayotgan voqea. Muayyan patogenning antijenlari tomonidan stimulyatsiya sodir bo'lgandan so'ng, antikor molekulalari va ularni chiqaradigan limfotsitlar miqdori ushbu patogen tomonidan qayta infektsiyani oldini olish uchun etarlicha yuqori bo'lib qoladi - ba'zida bu himoya hayotingizning oxirigacha davom etadi. Shuning uchun siz faqat bir marta ba'zi kasalliklarga duch kelasiz: masalan, qizamiq, parotit, suvchechak, poliomielit.

11) "emlash" organizmni patogen viruslar va bakteriyalarga qarshi ko'proq antitellar ishlab chiqarishni ataylab rag'batlantirishga asoslangan. Bu stimulyatsiyaga, odatda, tanani ataylab ushbu patogen organizmlarning antijenlari ta'sirida, izolyatsiyalangan antijenlar, o'ldirilgan patogenlar yoki hatto patogenlarning tirik, lekin zaiflashgan shakllari ta'sirida erishiladi.

12) Qadim zamonlarda ma'lum bo'lgan (tarixchi Fukidid bu haqda eslatib o'tadi) odamlar bir marta kasallanish natijasida ba'zi kasalliklarga moyil bo'lmaydilar. 1700-yillarda engil chechak bilan og'rigan odamlarni ataylab inkulyatsiya qilish g'oyasi Turkiyadan Meri Montegue tomonidan Angliyaga kiritilgan. Keyinchalik, Edvard Jenner odamlarga ataylab "sigir poxi" kasalligini yuqtirish bo'yicha xalq amaliyotini (deyarli barcha shifokorlar xurofot deb aytgan!) Qo'llab-quvvatladi. tegishli kasallik, chechak. (E'tibor bering, emlash so'zi ishqiy tilda "sigir" so'zidan kelib chiqqan, ispan tilidagi "vaca" kabi, emlash = "cowification").

13) Buyuk frantsuz olimi Lui Pasterning ko'plab yutuqlari orasida (1800 -yillarning oxirida) patogen organizmlarni emlash uchun ishlatish uchun ularni ajratish va ataylab zaiflashtirish protseduralari ishlab chiqilgan. Aks holda, bu yondashuv faqat kasallikning tegishli, ammo zaif shakli bo'lgan kasalliklar bilan chegaralanadi. Umuman olganda, u har qanday kasallik uchun "o'z sigir kasalini qilish" usullarini qidirgan.

14) Paster ishongan va shuning uchun uning tadqiqotiga turtki bo'lgan va yo'naltirgan immunitetni mexanik tushuntirish butunlay noto'g'ri edi! U tanada har bir ma'lum patogen organizmlarning o'sishi va omon qolishi uchun zarur bo'lgan turli xil iz elementlari borligiga ishongan va siz ushbu kasallikka chalinganingizda, bu mikroelementlar bu organizmlar tomonidan ishlatilgan deb hisoblagan, shuning uchun siz kasallikka sezilmas bo'lib qolgan deb hisoblagansiz. chunki tanangiz mikroblar yashashi uchun etarli miqdorda iz elementlarga ega emas. (E'tibor bering, noto'g'ri nazariyalar ba'zida to'g'ri bashorat qilishlari va tibbiy yutuqlarga olib kelishi mumkin!)

15) Keyinchalik ma'lum bo'lishicha, o'ldirilgan mikroblar va hatto ulardan ajratilgan oqsillar bilan in'ektsiya qilish (ba'zida) immunitetni keltirib chiqarishi mumkin. Ikkinchisining misoli, qoqshol va difteriya bakteriyalaridan ("toksoidlar") formaldegid bilan ishlangan oqsil toksinlaridan yasalgan vaktsinalardan foydalanishdir. E'tibor bering, "iz elementlarning kamayishi" gipotezasi faqat tirik mikroblar immunitet hosil qilishini bashorat qiladi. Ularning rivojlanishi taxminan 1900 yilda boshlangan.

16) Shuningdek, emlangan odamdan yoki hayvondan ajratilgan sarum in'ektsiya qilinganida immunitetni keltirib chiqarishi aniqlandi (bu "o'z immunitet molekulalarini ishlab chiqarish natijasida hosil bo'lgan" faol immunitet "dan farqli o'laroq," passiv immunitet "deb ataladi).

17) Oradan ko‘p o‘tmay (1900-yillarning birinchi o‘n yilliklari) qon quyishning (ko‘p yillar davomida sinab ko‘rilgan) ko‘pincha bunchalik halokatli natija bermasligining sababi shundaki, organizm quyiladigan qonga xuddi mikroblardek “hujum qiladi”. Ushbu kashfiyotlarda ishtirok etgan asosiy olimlardan biri Karl Landshtayner edi (u avstriyalik edi, lekin Birinchi jahon urushidan keyin Amerikaga kelgan).

18) Qonga qarshi immunitet (o'z turidan boshqa turdagi) oldingi ta'sir qilishni talab qilmaganga o'xshaydi (ilgari sizni "emlash" uchun quyish), "tabiiy antikorlar" mavjud deb ishonishgan, ularsiz ham ko'p miqdorda sintezlanadi. ularning antijeniga ta'sir qilishdan oldin har qanday. Haqiqiy tushuntirish shuni ko'rsatdiki, odamlarning qon guruhi antijenlariga juda o'xshash sirt antijenlariga ega bo'lgan bakteriyalarning hamma turlari mavjud, bu sizni ilgari qon guruhi antijenlariga sezgir qilgan.

19) Asr boshlanganidan keyin, har bir o'ziga xos antijenga qarshi antikorlarni sintez qilish qobiliyati, ota -bobolarimiz tabiiy tanlanish natijasida paydo bo'lgan meros bo'lib o'tgan qobiliyatga ega bo'lishi kerak, deb taxmin qilingan edi. X kasalligiga qarshi antikorlar bu kasallikdan o'lishga moyil bo'ladi, bu antikorlarni yaratish uchun genlarga ega bo'lganlar esa omon qolishga moyil bo'ladilar, shuning uchun har bir antikor hosil qiluvchi genlar populyatsiyada ko'payadi. Bu antikorlarning o'ziga xosligi uchun "selektsionizm mexanizmi" shaklidir. Bu juda oqilona taxmin, X. Uellsning "Dunyolar urushi" romanining tugashiga asos bo'lib xizmat qiladi. Aytgancha, Uellsning o'zi yozuvchi emas, balki tadqiqotchi -biolog bo'lishni juda xohlardi va fan doktori ilmiy darajasini oldi. biologiyada. Xuddi shu tushuntirish ko'pincha amerikalik hindularning Evropa kasalliklariga ko'proq moyilligi uchun beriladi. Bir paytlar bu haqiqat deb o'ylarmidingiz?

20) Seleksion mexanizmning mutlaqo boshqacha turini buyuk immunolog Pol Erlix taklif qilgan edi, bu yon zanjir nazariyasi bo'lib, u immun tizimining hujayralari o'z yuzalarida minglab maxsus molekulalar ("yon zanjirlar") bilan boshlanishi mumkin, deb taklif qildi. har biri boshqa shaklga ega va shuning uchun bu yon zanjirlardan biriga bog'langan antijen kelganda boshqa antijen bilan birlasha oladigan bo'lsa, u holda bu bog'lanish qandaydir tarzda hujayrani o'ziga xos yon zanjirni ko'paytirishga undaydi. Boshqa turlarni ishlab chiqarishni to'xtatish g'oyasi shundaki, antikor molekulalari yon zanjirlarning antigen bilan bog'lanish qobiliyati tufayli hujayralar rag'batlantirilgan yon zanjirlarning nusxalarini chiqaradi. Bu g'oya Jern va Bernetning keyingi klonal tanlov gipotezasini belgilab berdi va har xil nazariyalar o'rtasidagi o'xshashlik va farqlar diqqat bilan o'ylashga arziydi.

21) Ammo, birinchi jahon urushi paytida, Landshtayner tanasi juda sun'iy sintetik kimyoviy moddalarga qarshi antitelalar yasashi mumkinligini aniqladi. Chunki ota-bobolarimiz ushbu kimyoviy moddalarga duchor bo'lishlari mumkin emas edi (ularning omon qolishi va ko'payishi bunday kimyoviy moddalarga qarshi immunitetga bog'liq bo'lishi mumkin edi!), shuning uchun bu kuzatuvlar (noto'g'ri!) antikor molekulalari qandaydir tarzda bo'lishi kerakligini isbotlagandek tuyuldi. Bizning hujayralarimizga antikorlarni bog'lash joylari qanday shaklga ega bo'lishi kerakligi haqida "ko'rsatma bering" (qo'lqopda mos keladigan qo'lni topish o'rniga, ma'lum bir qo'lga mos keladigan qo'lqop yasash bilan teng). Agar siz poyafzal do'koniga borib, oyoqlaringizga to'g'ri mos keladigan poyafzallarni tanlasangiz, bu tanlangan mexanizmdir. Ammo do'kondagi odamlar sizning oyoqlaringizni o'lchab, keyin unga mos keladigan poyabzal ishlab chiqarishlari kerak bo'lsa, bu ta'lim mexanizmi.

22) "Ta'lim mexanizmlari": Bir xil aminokislotalar ketma -ketligini turli xil alternativ konformatsiyalarga qanday shakllantirish mumkinligini tushuntirish uchun bir necha turdagi gipoteza ishlab chiqilgan. Bunday ko'rsatmali nazariyalardan biri shundaki, antikor molekulalari sintez paytida qandaydir tarzda o'ralgan bo'lishi mumkin. Ligus Poling shunday nazariyani ilgari surdi va uni qo'llab -quvvatlovchi tajribalarni e'lon qildi. guruhlar juda koʻp turli xil muqobil almashtirishlarda bogʻlanishi mumkin va shu tariqa koʻplab turli antigen bogʻlanish joylari hosil boʻlishi mumkin.(Turli xil shakllar sonini hisoblay olasizmi?)

23) Ko'p o'tmay, 1960 -yillar davomida, agar siz antikor molekulasini denaturatsiya qilsangiz (aminokislotalar zanjirini ochsangiz va disulfid aloqalarini uzsangiz), so'ngra molekula o'z -o'zidan xohlasa, xohlagan naqshga qaytishiga yo'l qo'yganingiz isbotlangan. hosil bo'lgan antikor molekulasining bog'lanish joyi denatürasyondan oldin bo'lgani kabi bir xil o'ziga xoslik (antijen o'ziga xosligi) bo'ladi. Bu shuni ko'rsatadiki, antikor molekulalarining o'ziga xosligi ularning aminokislotalar ketma -ketligi bilan belgilanadi va aksincha, har xil spesifiklikka ega bo'lgan antikorlar har xil amino kislotalar ketma -ketligiga ega.

24-asrning 50-yillari oxirigacha, hamma aqlli, cherkovga boradigan immunologlar hali ham antikorlarning o'ziga xosligi haqidagi u yoki bu ko'rsatma nazariyalariga ishonishgan (antijen qandaydir tarzda tanaga antikor molekulasida bog'lanish joylari qanday shakl berishini "aytishi" kerak). Niels Jern ismli aqlsiz yigit tushuntirish gipotezasini taklif qildi, bunda tanlov ta'lim o'rnini egallaydi. Jern o'zining inqilobiy gipotezasini "immunitetning tabiiy tanlanish nazariyasi" deb atadi, lekin u tez orada Burnet tomonidan ixtiro qilingan "klonal selektsiya gipotezasi" deb nomlangan o'zgartirish bilan almashtirildi. (E'tibor bering, Jern Uotson bilan bir xil Daniya laboratoriyasida edi!)

25) Klonal tanlash gipotezasining asosiy g'oyalari quyidagilardan iborat: A) Embrion rivojlanish davrida har bir alohida hayvon (qandaydir!!) limfotsitlarning ko'p turli klonlarini hosil qiladi, ularning har biri boshqa antigenga qarshi antitellar hosil qiladi.
B) Har bir limfotsit faqat bitta o'ziga xos antijenga qarshi antikor ishlab chiqaradi va bu limfotsit bo'linib bo'lgach, qiz hujayralar o'ziga xos xususiyatlarga ega bo'lib, tasodifiy tanlangan antijeniga qarshi faqat antitelalar hosil qiladi.
C) Rivojlanish jarayonida limfotsitlarning "o'z" antigeniga (ularning antikorlari bog'laydigan) ta'sir qilishi, bu limfotsitlar klonlarining ("taqiqlangan klonlar") o'limiga yoki inaktivatsiyasiga olib keladi. Mexanizm o'z-o'ziga bag'rikenglikni shunday tushuntiradi.
D) Kechroq hayot davomida limfotsitlar "o'z" antijenlariga teskari javob qaytaradi, ular antikorlarning o'sishiga, bo'linishiga va sekretsiyasini rag'batlantirib, immunitet hosil qiladi.
E) Limfotsitlar klonlarining ko'pchiligi hech qachon "o'z" antijenlariga (ularning antikorlari bog'lanadigan) ta'sir qilmas edi, shuning uchun bu klonlar faol bo'lmagan holda omon qoladi.

Aytgancha, Jernning nazariyaning dastlabki versiyasiga instruktorlarning fikri shunchalik ta'sir ko'rsatdiki, u antikor molekulalari shakllangan shaklga ega bo'lgan kimyoviy shablonlarning klonlarini (antikorlarni sintezlovchi hujayralar klonlari emas) yaratish va tanlashni taqozo etdi! Shuning uchun biz Burnetni Jernening g'oyasini "o'g'irlagan" deb o'ylash adolatsiz bo'lar edi (lekin e'tibor bering, shvedlar buning uchun Nobel mukofotini Jerne emas, Bernetga berishgan, garchi u buni boshqa nazariyalar, jumladan, uning "o'g'irlashi uchun" keyinroq olgan bo'lsa ham. tarmoq nazariyasi "). Gor Vidal aytganidek: "Hech qachon Skandinaviya hazil tuyg'usini kamsitmang".

26) Klonal selektsiya gipotezasi embrionlarga antijenlarni yuborish orqali eksperimental ravishda sinovdan o'tkazildi va hayvon o'sha antijenlarga nisbatan bag'rikeng bo'lib qolganligini ko'rsatdi. Aynan shuning uchun Piter Medavar Nobel mukofotini Burnet bilan baham ko'rdi.

27) O'zgaruvchan ketma-ketlikdagi mintaqalar uchun genlarda millionlab xilma-xillikni keltirib chiqaradigan mexanizm (bir xil darajada) "xilma-xillik generatori" deb nomlangan. Ishonch bilan bashorat qilinganki, uning mexanizmini kashf qilgan kishi Nobel mukofotiga sazovor bo'ladi va uni kashfiyotchilardan biri 1987 yilda yutgan (Tonegava). Taklif etilgan gipotetik mexanizmlar ikkita asosiy toifaga bo'lindi: "germ liniyasi" va "somatik chiziq" nazariyalari, ammo haqiqiy javob ikkalasining g'alati aralashmasi bo'lib chiqdi.

28) Antikor molekulalarining aminokislotalar ketma -ketligini aniqlash juda qiyin edi, chunki juda ko'p turli xil antikor molekulalari oddiy odamning gamma -globulinlarini tashkil qiladi. Bu bir-biriga aralashgan turli xil fermentlarning butun to'plamining aminokislotalar ketma-ketligini aniqlashga urinish kabi edi (chunki turli antikorlar turli xil aminokislotalar ketma-ketligiga ega).
Bu muammo oddiy antikorlar o'rniga "Bence-Jones oqsillari" yordamida chetlab o'tildi. Bence-Jones oqsillari "ko'p miyelomli" saraton kasalligi bilan og'rigan bemorlarning qonida va siydigida yuqori konsentratsiyada uchraydi, bu B limfotsitlar saratoni va Bence-Jons oqsillari antikor molekulalarining bo'laklari bo'lib chiqadi. . Afzalligi shundaki, bu kasallikka chalingan har bir bemor uchun barcha Bens-Jons oqsillari bir xil aminokislotalar ketma-ketligiga ega. Buning sababi shundaki, har qanday bemordagi milliardlab saraton B hujayralarining barchasi saraton bilan o'zgartirilgan faqat bitta asl B hujayrasidan kelib chiqqan va bu saraton B hujayralarining barchasi xuddi shu asl o'zgartirilgan aminokislotalar ketma-ketligiga ega bo'lgan antikor molekulalarini chiqaradi. hujayra (ko'pincha bu asl ketma-ketlikning nuqsonli shakli bo'lsa ham). Qaysidir ma'noda, Bens-Jons oqsillari asl monoklonal antikorlardir. Ushbu Bens-Jons oqsillari taxminan 1850 yilda kashf etilgan, ammo ularning nima ekanligi 1960-yillarga qadar tushunilmagan. Ma'lum bo'lishicha, ma'lum bir sichqon shtammlarida ("Balb-C") saratonning bu shaklini coelomik bo'shliqlariga mineral moy quyish orqali qo'zg'atish mumkin. (!*&?)

29) Aminokislotalar ketma -ketligining bu va boshqa aniqlamalari shuni ko'rsatdiki, antikor molekulalarida ba'zi antikorlar molekulalari ketma -ketligi bir -biridan tubdan farq qiladigan, o'zgarmaydigan ketma -ketlik hududlari deyiladi. Ammo molekulaning ko'p qismi doimiy ketma-ketlik mintaqalaridan iborat bo'lib, ularda aminokislotalar ketma-ketligi bir antikordan ikkinchisiga (yoki bir Bens-Jons oqsilidan boshqasiga) bir xil bo'ladi. Bularga doimiy ketma -ketlikdagi hududlar deyiladi. Keyinchalik ko'rib turganimizdek, o'zgaruvchan ketma -ketlik hududlari bog'lanish joyini tashkil qiladi, doimiy ketma -ketlik esa molekulaning qolgan qismini hosil qiladi.

30) Bundan tashqari, antikor molekulalarining har xil turlari mavjud (immunoglobin G, immunoglobin M va boshqalar IgG, IgM, IgA, IgD va IgE deb qisqartirilgan). Ularning har biri bir oz boshqacha doimiy ketma-ketlik mintaqalariga ega. Aslida, ularning har biri turli xil oqsil molekulalarining birikmasidan iborat: masalan, har bir IgG molekulasi ikkita "og'ir zanjir" (har biri taxminan 50 000 molekulyar og'irlik) va ikkita "engil zanjir" (har biri taxminan 25 000 molekulyar og'irlik) dan iborat. . Har bir og'ir zanjirda 300 ga yaqin aminokislotalar va 100 ga yaqin aminokislotalarning o'zgarmaydigan ketma -ketlik mintaqasi mavjud. Har bir engil zanjirda 100 ga yaqin aminokislotadan iborat doimiy ketma-ketlik mintaqasi va 100 ga yaqin aminokislotadan iborat oʻzgaruvchan ketma-ketlik mintaqasi mavjud. 4 ta zanjir bir-biriga disulfid bog'lari bilan bog'langan.
Siz taxmin qilganingizdek, IgG molekulasining bog'lanish joyi bitta og'ir zanjir va bitta engil zanjirning o'zgaruvchan ketma-ketlik mintaqalarining birikmasidan hosil bo'ladi. Har bir IgG molekulasida ikkita bog'lanish joyi bor va ikkalasi ham o'ziga xos xususiyatga ega (bir epitopga bog'langan).

31) The IgM type of antibody molecule is even more complex, having 10 light chains and 10 heavy chains, with a total molecular weight of around 900,000. The structure is analogous to 5 IgG molecules combined together and they have 10 antigen binding sites instead of 2. When first exposed to an antigen, you at first synthesize mostly IgM, and then later you synthesize mostly IgG.
The other classes of immunoglobins (IgA, IgD and IgE) have 2 binding sites each.

32) Potential antigens will (usually!) not stimulate the immune system to synthesize antibodies unless the original antigens are parts of relatively large molecules (molecular weights of around 20,000 or more). Once the antibody molecules are made, however, they will bind perfectly well to antigens of low molecular weights (molecular weights as low as 100). An interesting example is the allergy which people sometimes develop to the antibiotic penicillin, even though it is a relatively small molecule the original sensitization to this compound depends on the fact that penicillin tends to bond covalently to proteins when attached to a protein, its effective molecular weight is then large enough to produce the needed stimulation of the immune system, although the antibody molecules which eventually result from this stimulation will also bind to individual penicillin molecules.
Thus, to immunize an animal against a small molecule, you usually need to combine the small molecule to some sufficiently big molecule. In addition, it is found that there are certain oily materials (called "adjuvants") which have the effect of increasing the sensitivity of the immune system to injected antigens, when they are injected mixed with the adjuvant.

33) When the immune system fails (or refuses!) to make antibodies against a certain antigen, this is called "tolerance" (or "immune tolerance"). Our day-to-day survival depends upon this refusal of our immune systems to attack the many thousands of potential antigens which are normal parts of our bodies. Failure of this self-tolerance in the case of even just one or a few of our normal constituent molecules results in autoimmune diseases, some of which were listed above: many are fatal.
One consequence of self-tolerance is that it can be difficult or impossible to stimulate animals to make antibodies against proteins which happen to be evolutionarily conservative, such as actin. The mechanism of self-tolerance remains one of the least understood aspects of immunity. A tendency to take tolerance for granted has long characterized the study of immunity.

    Question for class discussion: How could you try to explain self-tolerance in terms of either the original evolutionary selection type of explanation for immunity (#19 above), or in terms of the later instructional type of explanation (#22 above).

34) Monoclonal antibodies are made by growing clones of antibody-synthesizing lymphocytes in culture. Since the antibodies made by each lymphocyte and its mitotic progeny all have exactly the same amino acid sequence in their variable sequence regions, they all have exactly the same specificity. So you can get lots and lots of antibody molecules all of which have exactly the same specificity (exactly the same shaped binding sites). The essential trick was to fuse cancerous lymphocytes (immortal, fast-growing) with normal lymphocytes (slow-growing, but antibody synthesizing) one then selects progeny cells which both grow rapidly and secrete antibody molecules. Quite recently, people have isolated antibody genes and transformed them into bacteria.

35) The differences between B lymphocytes and T lymphocytes: It has been discovered that the effector cells of the immune system fall into two distinct categories. The cells that actually secrete the antibodies are B lymphocytes (or "B cells"), responsible for "humoral immunity". The "T cells", on the other hand, do not secrete antibodies but some of them produce equivalently specific binding proteins on their surface membranes ("called T cell receptors") that serve the analogous purpose in selectively killing cells that have antigens on their surfaces to which these reecptors will bind. This killing process has a degree of specificity approximately equivalent to that of antibody binding and is the central part of "cellular immunity".
In addition, there are other sub-classes of T cells whose functions are to control the activities of the B cells -sometimes by assisting in their sensitization to antigens, sometimes by stimulating them and sometimes by inhibiting them. T cells can function without B cells, but the B cell part of the immune system becomes non-functional if deprived of T cells. It is for this reason that people born without the B cell part of the immune system can survive much better than those born without the T cell part and it is also why the disease AIDS, which selectively kills a sub-class of T cell needed for the activation of killer T cells as well as B cells, results in the loss of both humoral and cellular immunity (and was the first evidence of helper T cells).
In general, one can say that resistance to bacterial infection is primarily the result of B cell (humoral) immunity, while resistance to viruses, fungi, protozoa and cancer are primarily the job of the T cell (cellular) immunity. The T cell system is supposed to have evolved first.

36) Graft rejection is believed to be largely due to the activities of T cells attacking the graft tissue, as opposed to being a result of the effects of antibodies. Likewise, the unpleasant effects of poison ivy are (supposedly) due to T cells: somehow the plant's toxin ("urushiol") changes exposed skin cells in such a way that T cells regard them as alien and therefore "reject" the skin cells as they would a graft. More needs to be known about this interesting phenomenon, and such knowledge may prove very useful not only for the treatment of poison ivy poisoning itself but also potentially for the deliberate use of this and comparable toxins to induce the rejection of cancerous cells.

37) There is a theory of "Immune Surveillance" according to which cancers actually arise much more frequently than we realize but that nearly all of them are killed off by the immune system before they can do any harm. This theory was originally proposed by none other than the well-known medical essayist Lewis Thomas and was very popular for several years before becoming somewhat passe. The most relevant supporting evidence is the much higher frequency of cancers which is observed in people whose immune systems are somehow suppressed (for example, by anti-rejection drugs following organ transplants, as well as in AIDS victims). Although this is exactly what the theory predicts, an alternative explanation is that the immune system is protecting us from cancer causing viruses and (perhaps) chemicals, rather than from already-transformed cells.

    Second set of questions for class discussion: How to use the immune system to reject cancer cells, even though they are part of the body itself. Actually, it is not unusual for a person's immune system to attack cancer cells. That may be the cause of many thousands of "spontaneous" cures of what had seemed incurable cancers? Much research has and is being focused on the possibility of stimulating immune attacks specifically on cancer cells, without attacking normal cells.
    a) But if the cancer cells are part of your body, why shouldn't your body be tolerant to them?
    b) And if cancer cells are often attacked by T-cells and antibodies, what does this imply about cancer cell antigens?
    c) How might the immune system be made more likely to attack "self" cancer cells?
    d) How might you try to increase the sensitivity of cancer cells to immune attack?
    e) Suppose that there were forms of uncontrolled cell growth in which the immune system always did successfully attack and destroy the abnormal cells: would such a disease be classified as a form of cancer?

39) It is believed that differentiation of B cells depends upon transient residence in some glandular organ (which thus serves the inductive maturation function equivalent to that served by the thymus for the T cells). In the case of birds, it was proven experimentally (although inadvertently) that this function is served by a diverticulum from their hindguts that is called the "Bursa of Fabricius". If this organ is prevented from developing then the resulting bird is unable to make antibodies because it has no B cells. In fact, the term "B" cells is derived from b in "bursa". Curiously, however, this organ is peculiar to birds and is not found in mammals so presumably some other organ serves the same function in mammals, possibly it might be the appendix, or the "Peyer's Patches", or the bone marrow itself, but no one knows. There is a widespread hope that the name of the organ responsible will happen to start with the letter B!
Animals lacking B cells cannot make antibodies, of course. This weakens, but does not eliminate their immune resistance to disease. Their T cells can still fight off many pathogens, as well as reject grafts, even without the help of B cells. In contrast, animals that lack the T cell part of the immune system have little or no immune capacity, even to make antibodies. This was once a puzzle but the explanation seems to be that the stimulation of the B cells to make antibodies depends on the B cells' interactions with certain kinds of ("helper") T cells. Of course, this is also what is believed to to be that basis of immune deficiency in AIDS.

40) The mechanism of the "Generator of Diversity": (G. O. D. as it was called)

The following is a list of some of the alternative hypothetical mechanisms that were seriously considered as possible explanations for how you get the genes coding for a million-plus different variable sequence regions (do you remember which one(s) turned out to be correct?):

A) There could simply be a million different antibody genes (i.e. in the eggs and sperm), each individual gene identical in the part coding for the constant sequence region, but each different (and unique) in the part coding for the variable sequence region.

B) The genome could contain a million different genes for just the variable sequence regions, with one of these being chosen at random (in each lymphocyte clone) and somehow spliced onto the gene for one of the different classes of constant sequence regions.

C) There could be a very, very high rate of somatic mutation in the part of the antibody gene that codes for the variable sequence region..

D) There might not actually be gene for the variable sequence region, at least not in the germ line cells or in cell types other than lymphocytes. Instead, as part of the differentiation, there might be some mechanism for random addition of nucleotides. The net result would be equivalent to the high rate of somatic mutation.

E) There might be only two different genes for the variable sequence region during the differentiation of lymphocytes, a process of genetic crossing-over (equivalent to that known to occur in meiosis) might occur between these two original variable sequence regions of DNA, even though these regions differed greatly in base sequence. Such crossing-over between genes of very different base sequences would thus generate many, many new sequences (although with certain predictable patterns of either/or regularity you might want to think about what sort of regularity this ought to have been!)

F) Different clones of lympocytes might have different populations of special t-RNAs with specificities different from those of the usual genetic code.

G) There might be some kinds of special base-altering enzymes that would act on the variable sequence regions of the m-RNAs coding for antibody molecules (with each lympocyte clone having a special set of such enzymes).

H) The variable sequence region of each the different antibody gene might be spliced together out of 2 or 3 randomly selected fragments from series of 4 - 100 (or so) alternative fragment sequences (perhaps something along the lines of "one from column A, one from column B,would you like a potato or rice. and which kind of dressing on your salad: French, thousand island. ).

Do you see why some types of theories (such as A and B) were sometimes called "germ line theories", to contrast them from other types of theories (such as C and D) that were called "somatic line theories"?

    Third set of questions for class discussion: Pretend that you don't already know which one of the 9 theories above turned out to be true (or maybe you don't have to pretend?), and discuss how each of the following sets of facts could be used to argue for or against these 9 alternatives.

(alpha) Mutations had been found that corresponded to amino acid substitutions in the constant sequence regions of the antibody molecules, and these mapped genetically in a simple Mendelian fashion, as if located at a single site on a particular chromosome

(beta) The total amount of DNA in a mammal genome would be barely adequate to code for several million different proteins of the molecular weight of the immunoglobins.

(gamma) The binding site of antibodies is formed along the zone of contact between the variable sequence of the heavy chain and the variable sequence of the light chain.

(delta) As a given animal responds to a particular antigen, it first makes mostly IgM antibodies against it, but later shifts to making mostly IgG antibodies with the same specificity. This occurs at the single cell level, in the sense of individual B-cells shifting from secreting IgM antibodies secreting IgG molecules (i.e. as if keeping the same variable sequence region, but shifting to a different constant sequence region).

(epsilon) Variable sequence regions from different myeloma clones were found to differ much more in some parts ("hypervariable regions") than in the rest.

(zeta) Except in the hypervariable regions, the amino acid sequence of variable regions from antibodies from different myeloma clones tended to fall into patterns in which each site was occupied by either of only 2 (or sometimes of only 3, or 4) different alternative amino acids. For example, at site #22, you might have valines in the antibodies from 8 of 14 myeloma clones, and leucines in the antibodies from the other 6 clones. Likewise, sequence of amino acids tend to be steroetyped, alternating between one particular sequence and another.

(eta) X-ray diffraction crystallography of antibody molecules shows that the variable sequences of both heavy and light chains consistently fold into beta pleated sheet patterns that are very similar to one another (even for antibodies against different antigens) except at the binding site itself (which is small relative to the whole variable sequence regions).

41) Histocompatibility antigens: A graft of tissue from one person to another (unless the two are identical twins) will almost always result in the "rejection" of the grafted cells by the immune system of the host, which attacks them much as if they were pathogens. Much research has been devoted to identifying which particular antigens are most responsible for this immune rejection of grafts (analogous to the A and B antigens, rhesus factors, etc. that are responsible for the analogous rejection of blood transfusions). A whole technology if "tissue typing" has been developed, analogous to the typing of blood. Unfortunately, it has turned out that there are a great many more different variable forms of genes which govern the graft rejection this means that the probability of finding a "match" between two individuals is enormously lower than is the case with blood. Imagine that instead of just having antigens A and B, our blood had A, B, C, . X, Y, and Z antigens, a difference in any one of which would result in an immune reaction.
Research on graft rejection has been concentrated in mice and humans. Ironically, this work began with grafts of cancers from one mouse to another as Medawar once wrote, "people started out thinking that they were using immunology to study cancer, but it turned out that they were really using cancer to study immunology"! Although there are many different molecules at the cell surface, and differences in any of these can potentially stimulate and be the targets of some degree of immune attack, it turned out that there are a few special classes of cell surface molecules which stimulate the immune system much more strongly than any others. These are called histocompatibility antigens, although the term has come to be confined specifically to those coded for by genes located in a cluster called the major histocompatibility locus. They have been most intensivily studied in mice, where they are called the H-2 antigens the equivalents in humans are called the HLA antigens.
In most species (in mice and humans, for example but not in Syrian hampsters) there are many alternative forms of these genes, thus reducing the chances of any 2 people being compatible and this situation is made still worse by the presence of multiple genetic loci in each set of chromosomes, so that each person has several different forms of the antigen, a situation which almost seems fiendishly designed to make tissue and organ grafting nearly impossible. Presumably there is no evolutionary selection pressure against the acceptance of tissue grafts (although some would answer that such selection pressures might have existed in some ancestral invertebrates, such as sea squirts or sponges). We therefore need to ask what functions these antigens have, of which graft rejection is an unfortunate by-product.
The answer was suggested by the structures of the major histocompatibility antigens themselves, which are very similar to antibody molecules and even have antigen binding sites that hold 10-20 amino acid peptides! It is now thought that their normal function is as a sort of molecular "holder" for the purpose of "presenting" partially digested fragments of potential antigen molecules to other cells of the immune system. This is part of the cell-cell signalling system by which the specificity of antibody-antibody binding is ascertained. Thus, when these holder molecules are themselves alien, the immune system responds with special diligence and ferocity.

    A) Why do most species have so many variant genetic forms in the population? B) Why is the possession of certain ones of these variant forms correlated with greatly increased probabilities of certain autoimmune diseases? C) Why are the genes for different forms of these antigens so closely linked to one another and to other genes which regulate the activity of the immune system, such as those for several lymphokines?

43) The activities of the various kinds of T and B cells are controlled by feedback cycles, many of which involve sending signals from one cell to another. The signaling mechanisms can be divided into two categories, those that involve direct contacts between cell surface molecules, and those that are accomplished by hormone-like proteins that are secreted by one cell and reach others by diffusion. These proteins are called "lymphokines", and around a dozen have been identified. Interferon is one of the best known (one should rather say, "the interferons" since there are 3 main kinds). The artificial synthesis of interferons and other lymphokines has been accomplished by cloning the genes for them into bacteria this is a very active area of pharmaceutical research because of the prospect of being able to control and manipulate the activities of the immune system. Interferons and several other lymphokines are now being used as experimental treatments for cancer, following more conventional chemotherapy. Unfortunately, the interferons produce the same side effects as having the flu fever, headache, aching joints, etc.! When you have the flu, your body is stimulated to produce lots of interferon, which is a large part of what makes you feel so bad.

44) A radically selectionist hypothesis about learning and the brain: You might be interested to know that Gerald Edelman, who shared the Nobel Prize for work on the molecular structures of antibodies, and later discovered new kinds of cell-cell adhesion proteins, has now moved on to neurophysiology. He has proposed a new and exciting hypothesis to explain how people learn new skills. He calls this new theory "Neural Darwinism" and has written a book with that title. His proposal is reminiscent of Jerne's and Burnet's, the basic idea being that the brain initially generates a large number of different neural wiring circuits (sort of like computer chips, or maybe pocket calculators) made with many different randomly-chosen wiring patterns, so that each circuit differs in capabilities. Edelman's idea is that these circuits play approximately the same role as the lymphocyte clones. Learning is then supposed to be selective, in the sense that each different circuit gets "tried out" to see which ones produce desirable consequences. The circuits that produce bad results are discarded or destroyed, while those that yield good results are kept and reduplicated. This may sound impractical or crazy, but so did clonal selection, at first. Do you think neurophysiology could now undergo a revolutionary paradigm switch from instructionism to selectionism?
There are some interesting parallels to Socrates' theory that education was a process of recalling of forgotten information, probably from previous reincarnations!! This notion was the original motivation for his famous "Socratic method" of teaching, although few people realize this.
Past thinking about learning has nearly all what one might call "instructionist", going back to John Locke's metaphor of the mind as "Tabula Rasa", Latin for "blank slate", on which experience writes things into your memory. Piaget's ideas also seem very "instructionist" to me. Learning is assumed to be a matter of putting something into the brain, or of creating something new there, as opposed to picking and choosing between different things that are already there (or differentially strengthening and weakening pre-existing patterns). On the other hand, Noam Chomsky, (MIT professor) revolutionized linguistics by providing strong evidence that babies and young children could not possibly learn correct grammar as rapidly as they do (i.e. having heard as few spoken sentences as they have) unless some kind of very abstract grammatical rules were already genetically programmed into the brain at birth (sort of like the ROM chip in a Macintosh computer!). Note that there would have to be one set of abstract rules for all languages. Several people have tried unsuccessfully to deduce what these rules might be. The great British zoologist J. Z. Young had previously proposed theories comparable to Edelman's "neural darwinism" based on many years of experiments on behavior and learning in captive octopuses!! Science moves along strange paths!

    Fourth set of questions for class discussion: What do you think goes on in your brain when you learn a new concept? Do you suppose that it's more like a multiple choice test, a true-false test, or a fill-in-the-blank? Are some people really smarter than others? Is it that smarter people have learned more that they can learn more or perhaps that they are faster or otherwise more skillful at learning? If Edelman were right, what would I.Q. be, at cellular and molecular levels?

1) Do you see why it is essential that each clone of B lymphocytes should make antibodies against only one single antigen (i.e. that all the antibodies made by a given clone should have exactly the same amino-acid sequences in their variable sequence regions)? Suppose that each lymphocyte clone made two different antibodies, with binding specificities for two different antigens. What would be some of the undesireable consequences of having some lymphocyte clones make more than one antibody? Would there be any advantages?

2) Mass epidemics of smallpox and other diseases decimated the native populations of the Americas soon after Columbus' voyages (and a comparable epidemic of syphilis occurred in Europe ). The usual explanation is that the natives had not "evolved immunity" to the germs. Is this consistent with current theories of immunity, or does it seem to reflect older assumptions? Discuss what the true explanation might be, whether this might require some further "revolution" in our theories, and what sorts of experiments or observations might be relevant to the question.

3) To what extent have the various theories of immunity conformed to Karl Popper's ideas about the best hypotheses being those that are most susceptible to disproof? Can you suggest some examples in which immunological theories now believed to be correct would once have actually seemed to have been conclusively disproven?

4) To what extent does the intellectual history of immunology conform to Thomas Kuhn's ideas? What were the different "revolutions" that occurred in this field, and what were the alternative "paradigms" that replaced one other? In particular, can you trace a "swing of the pendulum" back and forth between instructional and selectionist types of theories.

5) It has been said that "Any complicated phenomenonon has to be invented before anyone can discover it. Unless you have already considered the possible existence of a phenomenon, then how will you be able to recognize it even if you see it.?" Do you think that this is generally true in science? To what extent do you think that it may be true in daily life, in general? Can you give some examples, either from the history of immunololgy or from some other field, where this assertion seems to you to be true, or where it seems to be untrue? Do you think that maybe it tends to be more true of complex phenomena? If so, then how complicated does a phenomenon have to be before this statement becomes true?

6) Can you give some examples, either from immunology or from some other field, in which erroneous theories nevertheless made correct predictions.

    (a) immunity to diseases from which one has recovered.
    (b) allergy.
    (c) "immunity" to such things as poison ivy.
    (d) "immunity" to poisons which one has been exposed to repeatedly
    (as in the ancient story of King Mithridates, and in one of the Peter Wimsey murder mysteries).
    (e) reactions to blood transfusions.
    (g) graft rejection.
    (h) rejection of grafts of cancers from one animal to another.
    (i) occasional spontaneous recoveries from cancer.
    (j) accumulation of proteins in the urine of some lymphoma patients.
    (k) autoimmune diseases.
    (l) correlation of immunodeficiency syndromes with calcium imbalances.
    (m) failure of hair development in immunodeficient mice.

Another unsolved problem is how to use the immune system to kill cancer cells specifically. Because cancer cells are merely behaviorally-abnormal versions of your own cells, you should expect every animal to be just as self-tolerant to its own cancer cells as it is to all of its other cells. In fact, however, there is often evidence of immune attacks on tumors many cases of "spontaneous" remissions of cancer in humans seem to result from some activity of the immune system in addition, much medical research has been devoted to stimulating the immune system to attack cancer cells.
Injection of cytokines, more specifically interferons, following cancer chemotherapy, has been tried experimentally for about the past ten years, but with mostly disappointing (i.e. no) results.

In the specific cases of B-cell and T-cell lymphomas (almost? all Non-Hodgkin's lymphomas fall into one or the other of these categories), it is to be expected that all of the cancerous cells in a given patient will be members of a single original clone, so that their antibodies (in the case of B-cells) or their T-cell receptors (in the case of T-cells) will have binding sites of a given amino acid sequence and shape. Perhaps you can imagine cures based on inducting other cells of the immune system could to attack specifically any cells having surface molecules shaped like these binding sites (i.e. the binding sites specific to that particular person's lymphoma cells). Reading between the lines of some of the newspaper stories about former Chancellor Hooker's attempted "experimental treatment at Johns Hopkins" may have been based on this general approach. Newspapers strive to exclude factual information that some of its readers would not understand better nobody should know the facts than have some of the readers receive information they are not educated enough to understand?

A special class of T-lymphocytes is needed to stimulate the function of B-cells and other T cell. These "helper T-cells" are selectively killed by the AIDS virus, thereby weakening the whole immune system to the degree that the person dies of bacteria, fungi or other pathogens to which everyone is normally immune. Preventing this, or re-establishing helper T-cells, or perhaps substituting for their functions (in some other way stimulating B & T-cell function) are all possible ways of curing AIDS.

The specific enzyme(s) that serves to recombine the V(D)J sequences is called RAG. It is an important question when and where the genes for the RAG enzyme are expressed.

There have been reports that the RAG genes are expressed (=the messenger RNAs transcribed & the proteins made) only during the early development of B-cell and T-cells.

There have also been reports that RAG may be expressed in certain cells of the developing brain!

It has been controversial to what extent RAG genes may be expressed (& V(D)J recombination occur?) later in life in B cells as part of their response to exposure to their antigen! There is a report in this week's Nature that GFP (Green Fluorescent Protein) - RAG fusion genes are expressed in B-cells after antigen presentation. Copies of that paper will be handed out in the next class.


Is poison immunity actually attainable by poisoning the body repeatedly?

Sometimes, but it depends upon the poison/toxin/venom and how you define immune. That's exactly the process which is often used to produce snake antivenom. People will inject horses with small doses and build up a tolerance, then harvest their blood for the antibodies. Those horses are effectively immune to a normal snakebite. You could argue that a large enough dose would still be lethal so it's not complete immunity, but for practical purposes it is. I have run into stories of at least one person doing this to himself intentionally.

But you aren't going to be able to build up a resistance to mercury, for instance, because your body can't produce antibodies against it.

Your last sentence is a key point. Some poison will simply accumulate and eventually kill you.

That remind me of a quote, 'it's not the poison that kills you it's the dose'

The term for administrating sub-lethal amounts of a poison with the purpose of building up tolerance is called mithridatism. In practice it entails a lot of risk and is only effective against certain types of poisons, mostly those that are biologically complex that the liver metabolizes. Essentially this method is conditioning the liver to ramp up enzyme production. This doesn't give you immunity to the poison only increases the amount you have built up tolerance to. Where as poisons like heavy metals will not be metabolized and accumulate, this method will not be effective against these types of poisons.

Origin of the term is interesting, referring to Mithradates of Pontus

The Third Mithridatic War began in 75 BC, and ended with Mithridates’ final defeat and death in 63 BC. Following Mithridates’ defeat, he fled to his territories to the north of the Black Sea, where he faced a rebellion by his son. Cornered, Mithridates decided to take his own life. The following account is taken from Cassius Dio,

“Mithridates had tried to make away with himself, and after first removing his wives and remaining children by poison, he had swallowed all that was left yet neither by that means nor by the sword he was able to perish by his own hands. For the poison, although deadly, did not prevail over him, since he had inured his constitution to it, taking precautionary antidotes in large doses every day and the force of the sword blow was lessened on account of the weakness of his hand, caused by his age and present misfortunes, and as a result of taking the poison, whatever it was. When, therefore, he failed to take his life through his own efforts and seemed to linger beyond the proper time, those whom he had sent against his son fell upon him and hastened his end with their swords and spears."


Mithridatism is the practice of protecting oneself against a poison by gradually self-administering non-lethal amounts. The word is derived from Mithridates VI, the King of Pontus, who so feared being poisoned that he regularly ingested small doses, aiming to develop immunity.

So by that logic, if vaccines are poison, one should be able to protect themselves by getting immunizations!

Yes this is literally how vaccines for the most part work

Then if im not mistaken tried to kill himself with poison and it failed because of his immunity

Just chiming in to say that Mithridates did in fact succeed at attaining poison immunity. At great feasts he would dump poison on his food as a publicity stunt. To prove the poison was lethal he would then force a slave to eat it (dying soon after and proving how poisonous it was) then chow down in front of everyone like it wasn't anything. Many thought he was some kind of black magician king.

He as I remember, had to get a slave to chop his head off, the many bottles of poison wouldn't work, his kingdom was falling into enemy hands, he wasnt going down like that.

The book about him, “The Poison King,” is super fascinating. Apparently, he hatched a plot to have all of his subjects rise up en masse and murder any Roman settlers in their territory.

He managed to get the word out maintaining complete secrecy, and on the appointed day, the populace rose and slaughtered them. Tens of thousands died.

My favorite anecdote from that book was when he fed his ducks poison flowers, which they could tolerate, and then served them up at a feast, wiping out the whole guest list because the meat had absorbed so much toxins.

Not necessarily the first genocide,the first recorded genocide.

I just knew this would be here.

I’m reading a book called “Rubicon” right now and the author has just finished setting the table for his bigger confrontations with the Roman Republic. He mentioned the poison thing, too.

I first learned of Mithridates in a classic poem everyone should know:

Terence, This is Stupid Stuff

'Terence, this is stupid stuff: You eat your victuals fast enough There can't be much amiss, 'tis clear, To see the rate you drink your beer. But oh, good Lord, the verse you make, It gives a chap the belly-ache. The cow, the old cow, she is dead It sleeps well, the horned head: We poor lads, 'tis our turn now To hear such tunes as killed the cow. Pretty friendship 'tis to rhyme Your friends to death before their time Moping melancholy mad: Come, pipe a tune to dance to, lad.'

Why, if 'tis dancing you would be, There's brisker pipes than poetry. Say, for what were hop-yards meant, Or why was Burton built on Trent? Oh many a peer of England brews Livelier liquor than the Muse, And malt does more than Milton can To justify God's ways to man. Ale, man, ale's the stuff to drink For fellows whom it hurts to think: Look into the pewter pot To see the world as the world's not. And faith, 'tis pleasant till 'tis past: The mischief is that 'twill not last. Oh I have been to Ludlow fair And left my necktie God knows where, And carried half way home, or near, Pints and quarts of Ludlow beer: Then the world seemed none so bad, And I myself a sterling lad And down in lovely muck I've lain, Happy till I woke again. Then I saw the morning sky: Heigho, the tale was all a lie The world, it was the old world yet, I was I, my things were wet, And nothing now remained to do But begin the game anew.

Therefore, since the world has still Much good, but much less good than ill, And while the sun and moon endure Luck's a chance, but trouble's sure, Iɽ face it as a wise man would, And train for ill and not for good. 'Tis true, the stuff I bring for sale Is not so brisk a brew as ale: Out of a stem that scored the hand I wrung it in a weary land. But take it: if the smack is sour, The better for the embittered hour It should do good to heart and head When your soul is in my soul's stead And I will friend you, if I may, In the dark and cloudy day.

There was a king reigned in the East: There, when kings will sit to feast, They get their fill before they think With poisoned meat and poisoned drink. He gathered all the springs to birth From the many-venomed earth First a little, thence to more, He sampled all her killing store And easy, smiling, seasoned sound, Sate the king when healths went round. They put arsenic in his meat And stared aghast to watch him eat They poured strychnine in his cup And shook to see him drink it up: They shook, they stared as white's their shirt: Them it was their poison hurt.


Symptoms of COVID-19 Vaccine Damage

Many of the symptoms now being reported are suggestive of neurological damage. They have severe dyskinesia (impairment of voluntary movement), ataxia (lack of muscle control) and intermittent or chronic seizures. Many cases detailed in personal videos on social media are quite shocking.

Equally shocking is that these videos are quickly removed by the social media platforms, ostensibly for violating some term of service. It’s hard to fathom how a personal experience can be considered “false information.”

“What is causing this is the neuroinflammation,” Mikovits says. “It’s the brain on fire. You’re going to see tics, you’re going to see Parkinsonian disease, you’re going to see ALS, you’re going to see things like this developing at extremely rapid rates, and it’s inflammation of the brain.”

Side effects are also suggestive of a dysregulated innate immune response and a disrupted endocannabinoid system, which acts as a dimmer switch on your immune system.

“We see mast cell activation syndromes (MCAS). The clinical symptoms are going to be the inflammatory diseases. We hear everybody calling it ‘long haul COVID’ — the extreme, profound, crippling fatigue, the inability to produce energy from your mitochondria.

It’s not long haul COVID. It’s exactly what it always was — myalgic encephalomyelitis, inflammation of the brain and the spinal cord. What they’re intentionally doing is killing off [certain] populations, which they previously injured.”

Another common side effect from the vaccine we’re seeing is allergic reactions, including anaphylactic shock. A likely culprit in this is PEG, which an estimated 70% of Americans are allergic to. “These instantaneous effects are almost certainly the PEG and that lipid nano particle, the toxic particle that’s being injected,” Mikovits says.

In the longer term, she suspects we’ll see a significant uptick in migraines, tics, Parkinson’s disease, microvascular disorders, different cancers, including prostate cancer, severe pain syndromes like fibromyalgia and rheumatoid arthritis, bladder problems, kidney disease, psychosis, neurodegenerative diseases such as Lou Gehrig’s disease (ALS) and sleep disorders, including narcolepsy. In young children, autism-like symptoms are likely to develop as well, she thinks.


Allergic Contact Dermatitis

Dermatitis is an inflammation of the skin. If the allergy which causes the dermatitis is a response to something which came into contact with the skin, it is called allergik kontakt dermatit. In addition to poison ivy, other things which contact the skin such as clothing, shampoo, jewelry, make-up, and deodorants can also cause allergic contact dermatitis. Allergic dermatitis can also be caused from within, as when a skin rash develops because of something we ate.

An extensive list of substances causing allergic contact dermatitis has been provided by Truett.


What poisons can I safely take to build immunity to toxic substances? Does eating poison ivy build resistance to allergic reaction?

Dear Cecil:

I'd like to become resistant to one or more toxic substances by gradually increasing my intake of them over time. Unfortunately, many poisons build up in the body, usually in fatty tissue, until the concentration is lethal. Cecil, which poisons can I safely take in increasing quantities to build a resistance?

The Dread Pirate RobertsI've just been through my first-ever bout with poison ivy. Walking around with a bright red bumpy face has encouraged people to tell me of their remedies, but the strangest thing I heard was from two different people who told me that they'd eaten poison ivy to build up a resistance to it. Do people really do this? James Nelli, Columbus, Ohio

I’m seeing a problem right off the bat here, DPR, which is your use of the word “safely.” Deliberately exposing yourself to incrementally greater doses of poison (sometimes called mithridatization, after King Mithridates VI of Pontus, who reputedly pursued such a regimen) isn’t something that can really be done safely, any more than one can safely undertake to jump a nitro-burning funny car over a row of buses. Maybe you’ll make it, but the enterprise has a fair bit of risk built in.

To a limited extent, it is possible to build up a tolerance to certain poisonous metals. Metallothioneins are proteins produced in the body that, among other things, seem to bond to ions of dangerous elements like arsenic and cadmium and so help to minimize organ damage and other serious ill effects. While there’s no way to become immune to such poisons, chronic exposure to them may — I repeat, may — stimulate the body into upping its metallothionein output, thus allowing one to take on greater quantities of the toxic stuff before starting to get really sick.

Something along these lines might have been going on in the case of the famed arsenic eaters of Upper Styria, Austria. In the mid-1800s word got out to the wider world that a considerable percentage of Styrian peasants were ingesting potentially lethal quantities of arsenic (a by-product of the ore smelting going on thereabouts) on a regular basis, essentially as a health tonic — they believed it improved their breathing and complexion and helped them maintain a robust body weight. Many scientists scoffed, but academics familiar with the region vouched for the phenomenon. Fritz Pregl, a professor at the University of Graz, assured an American colleague in 1927 that arsenic eating was for real and remained common in Styria as of that time. The most popular delivery method, apparently, was to spread shavings of arsenic trioxide on a hunk of bread.

Some animal venoms may lend themselves to the mithridatic process as well. Several maverick herpetologists have reportedly developed partial immunity to various kinds of snakebite by injecting themselves with venom over a period of years the most famous of these is Bill Haast, for decades the proprietor of the Florida tourist attraction called the Miami Serpentarium (he still runs a venom lab under the name) and the survivor of something like 170 poisonous bites.

There’s a degree of self-selection in effect here, though. The people who embark on a long-term program of venom exposure aren’t, I’m guessing, the kind of people who first write to someone like me to ask if it’s a good idea. If you don’t already have a garage full of deadly reptiles from which you extract venom regularly, my suspicion is you’re not destined to get involved in any kind of venom-shooting scene.

But if you’re determined to become resistant to something unpleasant, you could always start with poison ivy. The active ingredient in poison ivy (as well as in poison oak and sumac) is the chemical urushiol, a nasty and persistent oil contained in almost every part of the plant contact with this stuff produces a serious allergic reaction in about 85 percent of the populace.

And as difficult as it may be to imagine doing, James, outdoors types have long advocated eating poison ivy leaves, in small amounts, as a way of building up one’s urushiol tolerance Euell Gibbons recommends the practice in his foraging guide Stalking the Wild Asparagus. Does it work? Dermatological testing says yes — ingesting urushiol made subjects less likely to break out in a rash following skin contact. The benefits decrease fairly quickly over time, so you have to keep up with it, and one noted side effect is pruritus ani, also known as itchy ass syndrome. You can also develop urushiol resistance via injections, or through occupational exposure — the oil is a key ingredient in traditional Japanese lacquer.

Minimizing your reaction to poison ivy doesn’t have quite the same dramatic flair as rendering yourself immune to actual poison, true, but it may prove more useful. Atmosferadagi CO2 miqdorining oshishi, tadqiqotchilarning ta'kidlashicha, yaqin kelajakda zaharli pechakning kattaroq va xavfli o'sishiga olib kelishi mumkin - bu global isishning yana bir qiziqarli chekkasi.